Vitamin D Improves Vascular Function
Researchers have added another reason to optimize vitamin D intake—prevention of heart disease and stroke.April 2019
By Julie Myers
Scientists discovered that, in a cell study, vitamin D restored a healthy balance between 2 key compounds required to maintain endothelial function.
The beneficial compound is nitric oxide that maintains youthful blood vessel elasticity. The toxic one is peroxynitrite that inflicts blood vessel damage.1-4
This study showed that the addition of vitamin D to the cell culture resulted in an increase in protective nitric oxide and a decrease in destructive peroxynitrite.4
Restoring this balance represents a novel approach to reducing overall risk for cardiovascular disasters.
Low blood levels of vitamin D are also associated with increased arterial stiffness—the loss of youthful suppleness that allows arteries to properly regulate blood flow and pressure.5
In addition to causing high blood pressure,6 stiff, inflexible arteries contribute to heart attack, stroke, cognitive decline, and more.7-11
More than 40% of Americans have insufficient blood levels of vitamin D (defined as less than 30 mg/dL).12
Supplementing with vitamin D helps reduce arterial stiffening and may improve endothelial function.5,13,14
What you need to know
- Arterial stiffness is a major risk factor for heart attack and stroke.
- Vitamin D has been shown to reduce arterial stiffness and may improve endothelial function.
- A recent study found that vitamin D restores the balance between protective nitric oxide, which is vessel-dilating, and peroxynitrite, a destructive free radical.
- This improves endothelial function, resulting in healthy blood flow and a healthy cardiovascular system.
- Life Extension® suggests daily supplementation with 5,000 to 8,000 IU of vitamin D3 and annual blood testing.
Vitamin D and Heart Health
Research shows a dangerous relationship between low vitamin D levels and heart failure, heart attacks, and high blood pressure.15 Low levels of vitamin D are also associated with cardiovascular risk factors such as obesity, diabetes, and lipid disturbances.16
When vitamin D was administered to rats with high blood pressure, it helped keep their aortas loose, relaxed, and able to move blood with minimal resistance.17
This suggests that there's a connection between vitamin D and how blood vessels respond to changes in flow and pressure.
A New Way to Improve Heart Health
Scientists at the Nanomedical Research Laboratory at Ohio University wanted to find out more about the connection between vitamin D and arterial function.4 Their findings take a giant step towards understanding the phenomenon of arterial stiffness.
The researchers used nanosensors to measure levels of 2 opposing chemicals inside of endothelial cells: nitric oxide and peroxynitrite. 4
Beneficial nitric oxide helps keep blood vessels dilated, while peroxynitrite is highly reactive and destabilizing.1-4
In an experiment, just before measuring nitric oxide and peroxynitrite levels, researchers treated endothelial cells with the human hormone angiotensin-II, which produced a state of endothelial dysfunction identical to that seen in living people.4
Initially, the distressed endothelial cells produced far too much of the destructive peroxynitrite and very little beneficial nitric oxide. This resulted in very low nitric oxide/peroxynitrite ratios (between 0.11 and 0.20), an indicator of endothelial dysfunction.4
But when tiny amounts of vitamin D3 were added, something remarkable happened.
In the presence of vitamin D3, the nitric oxide/peroxynitrite ratios immediately rose to between 2.1 and 3.0. That represented a more than 10-fold increase, restoring (and even exceeding) the normal ratio in healthy endothelial cells.
The improved ratio resulted from an increase in protective nitric oxide and a decrease in destructive peroxynitrite.4
This study suggests that vitamin D supplementation can restore normal endothelial function, supporting healthy blood flow and returning youthful suppleness to blood vessels.18
Arterial Stiffness: A Major Cardiovascular Risk Factor
Arterial stiffness is precisely what it sounds like. Numerous factors—such as aging, and exposure to oxidative stress, glycation, and inflammation—cause artery walls to lose their youthful elasticity and begin to behave more like stiff-walled pipes.19-22
As a result, instead of buffering the rapid rise in pressure following a heartbeat, old, stiff arteries transmit that pulse wave fast and hard to the organs they feed. Delicate organs, tissues, and cells are hammered by large fluctuations in blood pressure and flow with each heartbeat, which is harmful to their normal function.
In addition to contributing to hypertension, heart attacks, and strokes, arterial stiffness plays a role in kidney and liver disorders, type II diabetes, cognitive decline, and neurodegenerative disorders like Alzheimer's and Parkinson's.7-11
Vitamin D has properties that help reduce oxidative stress, glycation, and inflammation,23-27 suggesting that it may play a role in preventing the arterial stiffening induced by these age-accelerating events.
Compelling human studies show that vitamin D supplementation reduces arterial stiffness and blood pressure, directly reducing the risk of heart disease and stroke. As discussed next, in human cases where subjects have chronic kidney disease, obesity or type II diabetes, the addition of vitamin D lessened arterial stiffness.
Chronic Kidney Disease
In individuals with chronic kidney disease and vitamin D deficiency, supplementation with vitamin D caused arterial flow-mediated dilation to nearly double. Flow-mediated dilation is a measure of the ease with which arteries relax.
In addition, a marker of endothelial dysfunction (adhesion molecules that raise the risk of a clot forming or sticking) fell significantly.28
Studies of obese people who were vitamin D deficient showed similar findings.
In one study of overweight/obese adults with high blood pressure, a monthly oral dose of vitamin D3 (100,000 IU) for 3 months produced significant reductions in the augmentation index, a measure of arterial stiffness.29
A similar study showed significant reductions in pulse wave velocity, another measure of arterial stiffness. The higher the dose of the vitamin, the better the response.13
Type II Diabetes
Diabetes is known to produce increased arterial stiffness,30 and it is closely associated with vitamin D insufficiency.31 A study of type II diabetics showed that vitamin D supplementation significantly reduced arterial stiffness, as measured by pulse wave velocity.32
Benefits for Healthy Individuals
Even otherwise healthy people who have deficient or insufficient vitamin D levels benefit from supplementation.
In 2 studies of vitamin D-deficient individuals, vitamin D3 supplementation significantly reduced both systolic and diastolic blood pressure. It also reduced pulse wave velocity and augmentation index.33,34
A short study that used a modest dose of 2,000 IU daily in healthy individuals produced impressive results. Compared to baseline, in those receiving vitamin D3:35
- Arterial stiffness dropped by 18%,
- Systolic (top number) blood pressure fell by 8.2%, and
- Diastolic (bottom number) pressure fell by 9.1%.
And, in a study of healthy, older adults with vitamin D deficiency, a single intramuscular injection of 100,000 IU triggered a significant reduction in arterial stiffness (measured by augmentation index).36
New research into vitamin D3 indicates it is a heart-healthy vitamin.
Deficiency in vitamin D promotes arterial stiffness, which raises the risk of cardiovascular disease. Supplementation with vitamin D can prevent or reduce arterial stiffness.
One major way vitamin D accomplishes this is by restoring a healthy ratio between nitric oxide, which relaxes blood vessels, and peroxynitrite, a destructive free radical.
Since more than 40% of Americans have insufficient vitamin D levels, supplementation represents a major opportunity for improving public health and reducing cardiovascular risk.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
- Wattanapitayakul SK, Weinstein DM, Holycross BJ, et al. Endothelial dysfunction and peroxynitrite formation are early events in angiotensin-induced cardiovascular disorders. Faseb j. 2000 Feb;14(2):271-8.
- Zou MH, Cohen R, Ullrich V. Peroxynitrite and vascular endothelial dysfunction in diabetes mellitus. Endothelium. 2004 Mar-Apr;11(2):89-97.
- Forstermann U, Munzel T. Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation. 2006 Apr 4;113(13):1708-14.
- Khan A, Dawoud H, Malinski T. Nanomedical studies of the restoration of nitric oxide/peroxynitrite balance in dysfunctional endothelium by 1,25-dihydroxy vitamin D3 – clinical implications for cardiovascular diseases. International Journal of Nanomedicine. 2018;13:455-66.
- Al Mheid I, Patel R, Murrow J, et al. Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans. J Am Coll Cardiol. 2011 Jul 5;58(2):186-92.
- Thorin-Trescases N, Thorin E. Lifelong Cyclic Mechanical Strain Promotes Large Elastic Artery Stiffening: Increased Pulse Pressure and Old Age-Related Organ Failure. Can J Cardiol. 2016 May;32(5):624-33.
- Cardoso C, Salles G. Aortic Stiffness as a Surrogate Endpoint to Micro- and Macrovascular Complications in Patients with Type 2 Diabetes. International Journal of Molecular Sciences. 2016 Dec 6;17(12).
- Cheng HM, Park S, Huang Q, et al. Vascular aging and hypertension: Implications for the clinical application of central blood pressure. Int J Cardiol. 2017 Mar 1;230:209-13.
- Joly L. Arterial stiffness and cognitive function. Geriatr Psychol Neuropsychiatr Vieil. 2017 Mar 1;15(1):83-8.
- Villela-Nogueira CA, Leite NC, Cardoso CR, et al. NAFLD and Increased Aortic Stiffness: Parallel or Common Physiopathological Mechanisms? Int J Mol Sci. 2016 Apr 20;17(4).
- Wang M, Norman JE, Srinivasan VJ, et al. Metabolic, inflammatory, and microvascular determinants of white matter disease and cognitive decline. Am J Neurodegener Dis. 2016;5(5):171-7.
- Liu X, Baylin A, Levy PD. Vitamin D deficiency and insufficiency among US adults: prevalence, predictors and clinical implications. Br J Nutr. 2018 Apr;119(8):928-36.
- Raed A, Bhagatwala J, Zhu H, et al. Dose responses of vitamin D3 supplementation on arterial stiffness in overweight African Americans with vitamin D deficiency: A placebo controlled randomized trial. PLoS One. 2017;12(12):e0188424.
- Mazidi M, Karimi E, Rezaie P, et al. The impact of vitamin D supplement intake on vascular endothelial function; a systematic review and meta-analysis of randomized controlled trials. Food & Nutrition Research. 2017 2017/01/01;61(1):1273574.
- Giovannucci E, Liu Y, Hollis BW, et al. 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med. 2008 Jun 9;168(11):1174-80.
- Martins D, Wolf M, Pan D, et al. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2007 Jun 11;167(11):1159-65.
- Wong MS, Delansorne R, Man RY, et al. Chronic treatment with vitamin D lowers arterial blood pressure and reduces endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol. 2010 Oct;299(4):H1226-34.
- Sandoo A, van Zanten JJCSV, Metsios GS, et al. The endothelium and its role in regulating vascular tone. The open cardiovascular medicine journal. 2010;4:302-12.
- Gavish B, Izzo JL, Jr. Arterial Stiffness: Going a Step Beyond. Am J Hypertens. 2016 Nov 1;29(11):1223-33.
- Mozos I, Malainer C, Horbanczuk J, et al. Inflammatory Markers for Arterial Stiffness in Cardiovascular Diseases. Front Immunol. 2017;8:1058.
- Di Pino A, Currenti W, Urbano F, et al. High intake of dietary advanced glycation end-products is associated with increased arterial stiffness and inflammation in subjects with type 2 diabetes. Nutr Metab Cardiovasc Dis. 2017 Nov;27(11):978-84.
- Lessiani G, Santilli F, Boccatonda A, et al. Arterial stiffness and sedentary lifestyle: Role of oxidative stress. Vascul Pharmacol. 2016 Apr;79:1-5.
- Salum E, Kals J, Kampus P, et al. Vitamin D reduces deposition of advanced glycation end-products in the aortic wall and systemic oxidative stress in diabetic rats. Diabetes Res Clin Pract. 2013 May;100(2):243-9.
- Zhang Y, Leung DY, Goleva E. Anti-inflammatory and corticosteroid-enhancing actions of vitamin D in monocytes of patients with steroid-resistant and those with steroid-sensitive asthma. J Allergy Clin Immunol. 2014 Jun;133(6):1744-52 e1.
- Baser H, Can U, Baser S, et al. Serum total oxidant/anti-oxidant status, ischemia-modified albumin and oxidized-low density lipoprotein levels in patients with vitamin D deficiency. Arch Endocrinol Metab. 2015 Aug;59(4):318-24.
- Polidoro L, Properzi G, Marampon F, et al. Vitamin D protects human endothelial cells from H(2)O(2) oxidant injury through the Mek/Erk-Sirt1 axis activation. J Cardiovasc Transl Res. 2013 Apr;6(2):221-31.
- Tao S, Yuan Q, Mao L, et al. Vitamin D deficiency causes insulin resistance by provoking oxidative stress in hepatocytes. Oncotarget. 2017 Sep 15;8(40):67605-13.
- Chitalia N, Ismail T, Tooth L, et al. Impact of vitamin D supplementation on arterial vasomotion, stiffness and endothelial biomarkers in chronic kidney disease patients. PLoS One. 2014;9(3):e91363.
- Martins D, Meng YX, Tareen N, et al. The Effect of Short Term Vitamin D Supplementation on the Inflammatory and Oxidative Mediators of Arterial Stiffness. Health (Irvine Calif). 2014 Jun;6(12):1503-11.
- Weber T. Arterial stiffness, wave reflections, and diabetes: a bidirectional relationship? Am J Hypertens. 2010 Oct;23(10):1047-8.
- Pearce SH, Cheetham TD. Diagnosis and management of vitamin D deficiency. BMJ. 2010;340:b5664.
- Anandabaskar N, Selvarajan S, Dkhar SA, et al. Effect of Vitamin D Supplementation on Vascular Functions and Oxidative Stress in Type 2 Diabetic Patients with Vitamin D Deficiency. Indian J Endocrinol Metab. 2017 Jul-Aug;21(4):555-63.
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- Sunbul M, Cincin A, Bozbay M, et al. Arterial stiffness parameters associated with vitamin D deficiency and supplementation in patients with normal cardiac functions. Turk Kardiyol Dern Ars. 2016 Jun;44(4):281-8.
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